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Novel insights for SREBP-1 as a key transcription factor in regulating lipogenesis in a freshwater teleost, grass carp Ctenopharyngodon idella .
- Source :
-
The British journal of nutrition [Br J Nutr] 2019 Dec 14; Vol. 122 (11), pp. 1201-1211. - Publication Year :
- 2019
-
Abstract
- Disturbances in lipid metabolism are at the core of several health issues facing modern society, including fatty liver and obesity. The sterol regulatory element-binding protein 1 (SREBP-1) is one important transcription factor regulating lipid metabolism, but the relevant mechanism still remains unknown. The present study determined the transcriptional regulation of SREBP-1 and its target genes (including acetyl-CoA carboxylase α (accα), fatty acid synthase (fas) and stearoyl-CoA desaturase 1 (scd1)) in a freshwater teleost, grass carp Ctenopharyngodon idella. We cloned and characterised the 1988 bp, 2043 bp, 1632 bp and 1889 bp sequences of srebp-1, accα, scd1 and fas promoters, respectively. A cluster of putative binding sites of transcription factors, such as specific protein, yin yang 1, nuclear factor Y, sterol response elements (SRE) and enhancer box (E-box) element, were predicted on their promoter regions. Overexpression of nSREBP-1 reduced srebp-1 promoter activity, increased scd1 and fas promoter activity but did not influence accα promoter activity. The site-mutation and electrophoretic mobility shift assay analysis indicated that srebp-1, fas and scd1 promoters, but not accα promoter, possessed SRE. In Ctenopharyngodon idella kidney (CIK) cells of grass carp, nSREBP-1 overexpression significantly reduced srebp-1 mRNA expression and up-regulated miR-29 mRNA expression. The 3'UTR of srebp-1 possessed the potential miR-29 binding site and miR-29 up-regulated the luciferase activity of srebp-1 3'UTR and srebp-1 mRNA expression, implying a self-activating loop of SREBP-1 and miR-29 in grass carp. Based on the above-mentioned results, we found two novel transcriptional mechanisms for SREBP-1 in grass carp: (1) the auto-regulation sited on the SREBP-1 promoter regions was suppressive and (2) there was a self-activating loop of SREBP-1 and miR-29.
- Subjects :
- Acetyl-CoA Carboxylase genetics
Animals
Carps genetics
Cells, Cultured
Cloning, Molecular
Fatty Acid Synthases genetics
Gene Expression Regulation
Hep G2 Cells
Humans
Kidney chemistry
Kidney metabolism
Lipogenesis genetics
MicroRNAs genetics
MicroRNAs physiology
Mutagenesis, Site-Directed
Promoter Regions, Genetic genetics
Sequence Analysis, DNA veterinary
Stearoyl-CoA Desaturase genetics
Sterol Regulatory Element Binding Protein 1 genetics
Transcription, Genetic physiology
Transfection
Carps metabolism
Lipogenesis physiology
Sterol Regulatory Element Binding Protein 1 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2662
- Volume :
- 122
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The British journal of nutrition
- Publication Type :
- Academic Journal
- Accession number :
- 31782376
- Full Text :
- https://doi.org/10.1017/S0007114519001934